In this AREA application, the PI proposes to determine the mechanisms of beta 1-adrenergic receptor down regulation in the SK- N-MC cells. A unique feature of this cell type is that the beta1- adrenergic receptor expressed in this cell type does not appear susceptible to cAMP mediated down regulation. This may allow the applicant to study GRK induced down regulation in a straightforward manner. The applicant also proposes to determine the role of receptor phosphorylation in agonist induced down regulation.